DESIGN AND DEVELOPMENT OF 5 - FLUOROURACIL LOADED BIODEGRADABLE MICROSPHERES

The present study is aimed at the overall improvement in the efficacy, reduction in toxicity and enhancement of therapeutic index of 5-fluorouracil. Biodegradable microparticulate delivery system of 5-fluorouracil has been developed by solvent evaporation technique by using polymethacrylate polymers like eudragit L100, eudragit S100, eudragit P4135F and methylcellulose. Four different formulations were prepared by using these polymers in drug to polymer ratio of 1:2. The formulations were evaluated with respect to particle size analysis, entrapment efficiency, in vitro drug release studies, in vivo drug targeting studies and stability studies. The formulated magnetic microspheres were found to be spherical with average particle size of 3-12 µm in diameter and incorporation efficiency up to 78.80%. In vitro drug release after 12 hr was 86.41 %, 92.84 %, 79.88 % and 82.38 % for formulation F1, F2, F3 and F4 respectively. Formulation F2 with highest drug content was selected for in-vivo drug targeting studies. The average targeting efficiency of drug loaded microspheres was found to be 26.16 % of the injected dose in liver, 11.40 % in lungs, and 15.08 % in spleen, whereas the concentration of pure drug was 15.52 % in liver, 9.0 % in lungs, and 9.50 % in spleen. These results reveal that the drug loaded microspheres showed preferential drug targeting to liver followed by spleen and lungs. Stability studies revealed that 4o C is the most suitable temperature for storage of 5 fluorouracil loaded microspheres. Overall, this study showed that the 5 - fluorouracil can be formulated in a microparticulate drug delivery system by using various polymers and it showed significant prolonged drug release.